MEDLINE Journals

    Determination of water-soluble acid distribution in poly(lactide-co-glycolide).

    Authors
    Ding AG, Schwendeman SP 
    Institution

    Department of Pharmaceutical Sciences, College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109, USA.

    Source
    J Pharm Sci 2004 Feb; 93(2) :322-31.
    Abstract

    Determination of the kinetics of water-soluble degradation products inside poly(lactide-co-glycolide) (PLGA) delivery systems during polymer degradation is important to evaluate the polymer microclimate conditions, particularly microclimate pH changes for optimization of encapsulated drug stability. A pre-derivatization high-performance liquid chromatography (HPLC) method was developed for separation and quantification of water-soluble acid impurities and degradation products in PLGA. Thin PLGA films (approximately 200 microm) were incubated in PBS/0.02% Tween 80, pH 7.4, for 6 weeks. Water-soluble monomers and oligomers were obtained from polymer films after repeated CHCl(3)/H(2)O extraction and then derivatized into bromophenacyl esters. With the common chromophore, the esters were separated and quantified by HPLC with increased ultraviolet (UV) sensitivity at 254 nm. The total amount of water-soluble acids in the extract was validated by potentiometric titration with tetrabutyl ammonium hydroxide. During the first 3 weeks of incubation of PLGA 50:50 (inherent viscosity = 0.63 dL/g), the principal water-soluble acids in the polymer were glycolic, lactic, and lactoyllactic acids, and an unknown oligomer. After 4 weeks of incubation, a large fraction of higher molecular weight oligomers was observed. Pre-derivatization HPLC can be used to accurately measure water-soluble acid distribution, and may be invaluable to examine the degradation behavior of PLGAs, including the underlying mechanism of polymer microclimate pH development.

    Mesh
    Acids
    Chromatography, High Pressure Liquid
    Electrodes
    Excipients
    Indicators and Reagents
    Lactic Acid
    Magnetic Resonance Spectroscopy
    Mass Spectrometry
    Membranes, Artificial
    Polyglycolic Acid
    Polymers
    Potentiometry
    Reference Standards
    Solubility
    Water
    Language

    eng

    Pub Type(s)
    Journal Article Research Support, U.S. Gov't, P.H.S.
    PubMed ID

    14705190

    Content Manager
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